It is well established that varicella-zoster infection in patients with neoplastic disease frequently is accompanied by severe dissemination, post-herpetic neuralgia and a significant mortality rate. The well-documented antiviral effects of double-stranded polyribonucleotides in various animal model systems provided the rationale for our use of polyinosinic-polycytidylic acid (rIn.rCn) as a therapeutic agent in such patients. In preliminary pharmacological studies on man, 22 patients with viral disease were treated with escalating doses of rIn.rCn. Twenty of the 22 patients were cancer patients mostly with lymphoma and acute lymphocytic leukemia and receiving chemotherapy. Interferon responses were noted generally at doses of rIn.rCn above 3 mg/kg. Toxicity consisted of mild elevations of liver enzymes noted in 10 patients and slight abnormalities of coagulation noted in 7 patients. Fever was noted in 19 patients. Apparent clinical response were noted in 17 patients; two additional cases showed questionable response, and there were 3 failures. We have closely monitored several parameters of antiviral activities, toxicities, and clinical responses after rIn.rCn, and have established general patterns as to how these responses relate to drug dosage. We now propose a randomized, double-blind study in cancer patients with zona zoster in which half the patients will receive rIn.rCn and the other half a placebo-type injection. The patients will be evaluated primarily on clinical response, various toxicities and antiviral responses, including antibody levels and serum and vesicle fluid interferon levels. The overall objective is to determine whether rIn.rCn can control herpes zoster virus infection in man, and to determine the role that the interferon response may play in this control. We will also document rate-limiting toxicities; our structure-function studies (Carter and DeClercq, 1974) might then lead to the development of a superior therapeutic agent.